Incidence of pseudoprogression in low-grade gliomas treated with radiotherapy.

Background: As the incidence of pseudo-progressive disease (psPD), or pseudoprogression, in low-grade glioma (LGG) is unknown, we retrospectively investigated this phenomenon in a cohort of LGG patients given radiotherapy (RT). Methods: All MRI scans and clinical data from patients with histologically proven LGG treated with radiation between 2000 and 2011 were reviewed. PsPD was scored when a new enhancing lesion occurred after RT and subsequently disappeared or remained stable for at least a year without therapy, including dexamethasone. Results: Sixty-three out of 71 patients who received RT for LGG were deemed eligible for evaluation of psPD. The median follow-up was 5 years (range 1‒10 y). PsPD was seen in 13 patients (20.6%). PsPD occurred after a median of 12 months with a range of 3-78 months. The median duration of psPD was 6 months, with a range of 2-26 months and always occurred within the RT high dose fields of at least 45 Gy. The area of the enhancement at the time of psPD was significantly smaller compared with the area of enhancement during "true" progression (median size 54mm2 [range 12-340mm2] vs 270mm2 [range 30-3420mm2], respectively; P = .009). Conclusions: PsPD occurs frequently in LGG patients receiving RT. This supports the policy to postpone a new line of treatment until progression is evident, especially when patients have small contrast enhancing lesions within the RT field.

A phase II study of paclitaxel in advanced bronchioloalveolar carcinoma (EORTC trial 08956).

PURPOSE: The incidence of bronchioloalveolar carcinoma (BAC) has risen steadily over the last decades along with the increasing frequency of adenocarcinomas. BAC is relatively resistant to commonly used chemotherapy regimens. A phase II study with single agent paclitaxel in patients with stages IIIB, IV or recurrent BAC was performed. EXPERIMENTAL DESIGN: Patients with BAC with at least one target bidimensionally measurable lesion staged as unresectable stages IIIB, IV or recurrent disease, not previously irradiated; ECOG performance status 0-2; life expectancy greater than 3 months; age range between 18 and 75, received paclitaxel at a dose of 200 mg/m2 i.v. as 3h continuous infusion on day 1 every 21 days. Treatment was continued until progression or up to a maximum of six cycles. RESULTS: Nineteen patients were eligible. Median number of cycles was 3 (range 0-6); 35% of patients received the planned six cycles of chemotherapy. One patient died of unrelated cause before the start of treatment. Both hematological and non-hematological toxicities were generally mild. Only one partial response (PR) was observed among the 18 eligible patients who started protocol treatment, with a response rate of 5.6% (95% CI: 0.1-27.3%). After an independent review, two PR were confirmed, for a response rate of 11.1% (95% CI: 1.4-34.7%); nine patients had stable disease (50.0%), three patients had progressive disease (11.1%) and four patients were not assessable (22.2%). Median survival was 8.6 months (95% CI: 5.8-14.5) and 1-year survival was 35.0% (95% CI: 14.1-55.8). Median progression free survival for all patients was 2.2 months (95% CI: 1.5-6.0). The study was terminated due to the low response rate. CONCLUSIONS: Paclitaxel as single agent in stages IIIB-IV BAC was well tolerated and manageable but of limited efficacy. BAC should not be excluded from trials of new forms of chemotherapy.

Liver and vertebral uptake of Tc-99m macroaggregated albumin (MAA).

An unusual phenomenon during lung scintigraphy is presented. Besides visualization of the lungs, accumulation of Tc-99m macroaggregated albumin (MAA) was seen in a small part of the liver and in and around several thoracic vertebrae. Contrast-enhanced radiographic computed tomography revealed extensive collateral pathways, which were caused by a partially obstructed superior vena cava. Shunting of systemic venous blood flow through chest wall veins to the portal system was responsible for accumulation of MAA in the liver. Retrograde blood flow through dilated thoracic vertebral veins resulted in visualization of the bone marrow.

Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide.

BACKGROUND: Radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) is now the standard of care for patients with newly diagnosed glioblastoma. The occurrence of pseudo-progression directly after RT is a recognized phenomenon, but to the authors' knowledge its incidence after combined RT/TMZ is unknown. The occurrence of early pseudo-progression was retrospectively assessed in a cohort of malignant glioma patients treated with RT/TMZ. METHODS: The pre-RT and post-RT brain scans from patients treated with RT/TMZ for a malignant glioma were reviewed. Scans were made before the start of RT, 4 weeks after the end of RT, and every 3 months thereafter. In addition, information was collected regarding clinical signs and symptoms, dexamethasone dose, histology, and survival. RESULTS: Eighty-five patients were identified. In 36 patients (42%) the first follow-up scan 4 weeks after the end of RT indicated disease progression. Of these 36 patients, 18 (50%) were diagnosed with pseudo-progression. None of the patients received additional treatment other than TMZ. Six of 18 patients with pseudo-progression and 12 of the 18 patients with real tumor progression developed new clinical signs and symptoms during RT or in the first 4 weeks thereafter. CONCLUSIONS: Up to 50% of malignant glioma patients treated with RT/TMZ and progression immediately after RT develop pseudo-progression. The current study data support the idea to continue TMZ in the case of progressive lesions immediately after RT/TMZ. Surgery should be considered in symptomatic cases. The inclusion of patients with progressive lesions developing directly after chemoradiation in studies regarding recurrent gliomas will lead to an overestimation of the results.

Successful treatment of low-grade oligodendroglial tumors with a chemotherapy regimen of procarbazine, lomustine, and vincristine.

BACKGROUND: Anaplastic oligodendroglioma (OD) tumors, especially those with the combined loss of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), are sensitive to chemotherapy. Only limited data are available on the role of chemotherapy in low-grade OD. The authors retrospectively studied the outcome of the procarbazine, lomustine, and vincristine (PCV) chemotherapy regimen in a group of 16 patients with newly diagnosed OD and 5 patients with recurrent low-grade OD. METHODS: Two groups of patients were studied: newly diagnosed patients with large OD and mixed oligoastrocytomas (OA) and patients with recurrent OD and OA after radiotherapy who still showed nonenhancing tumors. Treatment consisted of standard PCV chemotherapy. In the newly diagnosed and responding patients, radiotherapy was withheld until the time of disease recurrence. Responses were assessed by T2-weighted magnetic resonance image (MRI) scans. Loss of chromosome 1p and 19q was assessed using fluorescent in situ hybridization with locus-specific probes. RESULTS: Three of five patients with recurrent tumors responded. Thirteen of the 16 newly diagnosed patients showed evidence of response. The median time to disease progression in this group was >24 months. Only one of these patients experienced disease progression while receiving chemotherapy. Several patients showed a signficant clinical improvement despite only a modest improvement of the tumor on the MRI scans. Even patients without loss of 1p or 19q showed satisfactory responses. No TP53 mutations were found. CONCLUSIONS: Newly diagnosed patients with OD tumors, with or without loss of 1p/19q, responded to PCV chemotherapy. Up-front chemotherapy may be indicated especially for patients with large tumors. MRI scans were of limited value for the assessment of response. A Phase III trial should be initiated to compare radiotherapy with chemotherapy.